Publication: Thymic alterations induced by partial
hepatectomy: upregulation of glycoprotein 96,
CD91 and TLR2 and generation of regulatory T cells
Authors
Jakovac, Hrvoje ; Ćuk, Mira ; Trobonjača, Zlatko ; Mrakovčić-Šutić, Ines ; Radošević-Stašić, Biserka
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
https://doi.org/10.14670/HH-11-597
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info:eu-repo/semantics/article
Description
Abstract
Glycoprotein 96 (gp96) is an endoplasmic
reticulum (ER)-resident heat shock protein. It controls
the folding of nascent membrane-spanning and secretory
proteins, participates in stress-induced unfolded protein
response (UPR) and in pathways leading to proteolysis
of damaged proteins through ER-associated degradation
pathways and chaperone-mediated autophagy. In
addition, gp96 controls the steroid biosynthesis and Ca2+
homeostasis and participates in insulin-IGF/signaling
pathways. Besides, owing to its peptide chaperone
capacity and ability to interact with antigen-presenting
cells, gp96 has been implicated in priming of innate and
adaptive immunity.
In an attempt to visualize the intensity of ER-stress
in thymus and possible participation of gp96 in
generation of auto-reactive T cell clones that were
detected in regenerating liver, in this study we
investigated the dynamics of gp96 expression in partially
hepatectomized (pHx) and sham Hx mice.
Simultaneously, we detected the thymic expression of
receptors responsible for endocytosis of gp96-
chaperoned peptides (CD91) and intracellular activation
of ER-stress pathways (TLR2), as well as the expression
of TGF-β and the distribution of CD4+CD25+FoxP3+
cells. The data have shown that both pHx and sham Hx
induced an accelerated apoptosis and hypoplasia in
thymus. Partial Hx induced, however, a higher
expression of gp96, the translocation of the CD91, TLR2
and TGF-β immunostaining from medulla to cortex and an appearance of Treg cells.
The data show that pHx triggers in thymus the ERstress and UPR response and suggest that gp96
participates in the generation of natural Treg cells, which
might be involved in the control of liver regeneration in
the periphery.
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Citation
Histology and histopathology, Vol. 30, nº 8 (2015)
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